The "Acquired Immunodeficiency Syndrome" (AIDS) is a disorder characterized by a severe disturbance of cell mediated immunity that leads to opportunistic infections or unusual neoplasms such as Kaposi's sarcoma or malignant lymphomas in previously healthy individuals. A chronic lymphadenopathy syndrome often precedes or accompanies the development of AIDS. There is considerable debate as to whether this newly recognized epidemic is triggered by a novel viral agent or can be accounted for solely by continuous active infections with a combination of familiar agents encountered by those at highest risk, primarily promiscuous male homosexuals. Exposure to high levels of CMV is an unusual and constant feature of the lifestyle of those in high risk group and CMV has been previously linked to development of Kaposi's sarcoma. Recent findings now indicate that although all homosexuals AIDS patients are seropositive to numerous viral agents they are actively shedding high levels of both EBV and CMV. Furthermore, EBV antigens can be detected in Kaposi's sarcoma tumors and in TPA-induced endothelial cell lines. We have obtained preliminary evidence for the presence of EBV genomes in both Kaposi's sarcoma containing lymph node biopsies and cultured KS cell lines established by Dr. G. Quinnan's group at the FDA. The notion that simultaneous active infection with these two herpesviruses (perhaps triggered by some other viral agent or immunological insult) may cause AIDS has considerable attractions. Therefore, we propose to further examine the extent and significance of the association of EBV and CMV DNA with Kaposi's sarcoma and lymphadenopathy samples by Southern DNA blots and in situ RNA hybridization procedures using high sensitivity cloned DNA probes and to use a simple DNA hybridization system for rapid detection and comparison of EBV and CMV virus shedding in healthy homosexuals and AIDS patients. Analysis of the state, structure, and levels of gene expression of the viral genomes in Kaposi's sarcoma tissue and in KS cell lines and also in lymphocyte cell lines derived from AIDS patients will be carried out and the possibility that a new, unusual or altered EBV is present will be examined carefully. Specific interactions between CMV and EBV in endothelial cells and other appropriate cell cultures after dual infection with both viruses will also be examined.